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E. A. Spencer, S. S. Samudre, F. A. Lattanzio, Jr., P. B. Williams; Comparison of the Pharmacokinetics of WIN 55212-2 and Latanoprost in the Human Cornea Versus the Human Sclera. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3163.
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© ARVO (1962-2015); The Authors (2016-present)
WIN55-212-2 (WIN), a cannabinoid, reduces IOP and retinal degeneration in a rat glaucoma model. Pharmacokinetics of 3H-WIN55-212-2 and 3H-latanoprost (Xalatan®), the leading glaucoma therapy) were compared. We hypothesized that drug penetration through human sclera would be similar to the cornea.
Human corneas and sclerae were each mounted in an Ussing chamber with the epithelium facing the outer chamber of the apparatus. Scleral thickness measurements were determined by image analysis of edge on scleral preparations recorded via digital camera on a slit lamp. Admixtures of either 3H-WIN (1.0 - 0.125%, dissolved in TocrisolveTM) or 3H-latanoprost (0.05 - 0.0005%, mixed with sterile PBS) were added to the outer chamber to simulate topical administration in the human eye. Drug admixture concentrations were selected as those achieving a therapeutic response in rats (WIN) and humans (latanoprost). Samples were collected at baseline, 1, 2, 3, 4, 20 and 24 hrs through a sampling port in the internal chamber. Samples were then assayed for radioactivity by scintillation counting. Results are expressed as nM/hour.
Drug transport for 3H-WIN after 24 hrs through the cornea was 1.6, 2.0 and 2.0 nM/hr for 1.0%, 0.5% and 0.125% respectively. Similarly for the sclera, drug penetration was 1.6, 1.8 and 1.7 nM/hr. Drug transport after latanoprost was 1.6, 1.1 and 0.6 nM/hr through the cornea and 1.1, 1.0 and 1.0 nM/hr through the sclera (0.05%, 0.005% and 0.0005% respectively). Average corneal endothelial cell density was approximately 3000 cells. The thickness was 0.5 mm for the cornea and 0.6 mm for sclera. The exposure area for both cornea and sclera was 28mm2.
For both drugs, transport through sclera was similar to that through cornea. Although the dose of latanoprost was 20x less than WIN, transport across cornea and sclera was comparable for both drugs. A significant drug concentration-transport relationship was not apparent, except for lantanoprost transport across the cornea. The scleral drug delivery route would be preferred because (1) drugs crossing the sclera travel through fewer compartments to reach the retina, (2) the larger vascular circulation and scleral surface area (and hence greater drug reservoir capacity), (3) the removal of temporary corneal optical distortion and negative impact of high drug/preservative concentrations on the cornea.
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